RESUMO
Death of retinal photoreceptors is the basis of prevalent blinding diseases. Since steroids might have a therapeutic role in retinal degenerations, we compared the protective effects of dexamethasone and progesterone on photoreceptor death induced by mifepristone and light exposure. Therefore, we studied the effective protection doses for each steroid in the two models. In addition, we analyzed changes in the levels of pro- and antiapoptotic molecules, glucocorticoid receptors α and ß (GRα and GRß), and rhodopsin under conditions of successful protection and photoreceptor survival. Mifepristone and light exposure selectively damaged photoreceptors. In light exposed retinas, photoreceptors mainly disappeared in the dorsotemporal region, while mifepristone produced a uniform damage. Dexamethasone and progesterone, at the same dose of 4â¯mg/kg/day for 2 days, preserved over 88% photoreceptor nuclei in both models. Assessment of cell death regulators showed that, in control retinas, both steroids activated BCL-XL, a prosurvival molecule, and decreased BID, a proapoptotic regulator. After steroid treatment of damaged retinas, BCL-XL, BCL2 and BAX showed characteristic patterns depending on the use of dexamethasone or progesterone on mifepristone or light exposed retinas. By contrast, BID decreased with any injury-steroid combination. Changes in GRα or GRß levels did not correlate with survival but were consistent with a mechanism of ligand induced downregulation of receptor expression. GRß might be upregulated by progesterone. Both dexamethasone and progesterone increased retinal rhodopsin stores, suggesting a link between photoreceptor protection and transduction pathways. Results show that dexamethasone and progesterone induced comparable but not identical protection responses in each model.
Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Progesterona/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Degeneração Retiniana/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Western Blotting , Caspase 3 , Sobrevivência Celular/fisiologia , Antagonistas de Hormônios/toxicidade , Imuno-Histoquímica , Luz/efeitos adversos , Masculino , Camundongos Endogâmicos BALB C , Mifepristona/toxicidade , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Receptores de Glucocorticoides/metabolismo , Degeneração Retiniana/etiologia , Degeneração Retiniana/metabolismo , Rodopsina/metabolismo , Proteína bcl-X/metabolismoRESUMO
PURPOSE: The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. METHODS: We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR. RESULTS: We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and Cfd, were all upregulated after light exposure. Retinal Iba1-positive microglia/macrophages express receptors for C3a and C5a. Light damage increased the number of retinal Iba1-positive cells and the mRNA levels of Iba1. Compared with the wild-type (WT) mice, these increases were attenuated in the C5aR KO mice but not in the C3aR KO mice. CONCLUSIONS: C5aR but not C3aR promoted the recruitment of microglia/macrophages. These divergent properties of complement anaphylatoxins in the light damage model provide a rationale for testing the differential effects of these receptors in additional retinal and neurodegeneration models.
Assuntos
Movimento Celular/efeitos da radiação , Técnicas de Inativação de Genes , Luz/efeitos adversos , Macrófagos/fisiologia , Microglia/fisiologia , Receptor da Anafilatoxina C5a/genética , Degeneração Retiniana/patologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , RNA Mensageiro/genética , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/patologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores Acoplados a Proteínas G/genética , Retina/efeitos da radiação , Degeneração Retiniana/etiologiaRESUMO
OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1). RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. CONCLUSION: Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.
Assuntos
Terapia por Captura de Nêutron de Boro/efeitos adversos , Histamina/uso terapêutico , Neoplasias Bucais/radioterapia , Lesões Pré-Cancerosas/radioterapia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Estomatite/prevenção & controle , Animais , Cricetinae , Modelos Animais de Doenças , Indóis/uso terapêutico , Piperazinas/uso terapêutico , Lesões Experimentais por Radiação/etiologia , Estomatite/etiologiaRESUMO
PURPOSE: To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development. MATERIALS AND METHODS: Hamsters' cheeks were treated with Co-60 radiation (10, 20, 30 or 35 Gy). Three days later, oral mucosa scarification was performed with a needle. The animals were euthanized at day 13 (D + 13) after irradiation. Gross and microscopic alterations were evaluated by a new score system that we developed. Also, neutrophil infiltration, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-10, inducible nitric oxide synthase (iNOS), nitric oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish the roles of TNF-α and IL-1ß and iNOS in our model using pharmacological approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively. RESULTS: We found that a single administration of 35 Gy of Co-60, followed by mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals with mucositis lost weight and had a survival median of 13 days, the time at which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF-α and IL-1ß and a reduced concentration of IL-10. PTX partially prevented the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60-induced oral mucositis through reducing NO production. CONCLUSION: We described a novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF-α, IL-1ß and NO seem to play a role in the pathophysiology of this model.
Assuntos
Citocinas/metabolismo , Óxido Nítrico/metabolismo , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Estomatite/etiologia , Estomatite/metabolismo , Animais , Radioisótopos de Cobalto/efeitos adversos , Cricetinae , Modelos Animais de Doenças , Guanidinas/farmacologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Mesocricetus , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Pentoxifilina/farmacologia , Peroxidase/metabolismo , Lesões Experimentais por Radiação/imunologia , Radioterapia de Alta Energia/efeitos adversos , Estomatite/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. MATERIALS AND METHODS: Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. RESULTS: Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). CONCLUSION: Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.
Assuntos
Telefone Celular , Cistite/etiologia , Radiação Eletromagnética , Doenças da Bexiga Urinária/etiologia , Animais , Masculino , Microscopia Eletrônica de Transmissão , Lesões Experimentais por Radiação/etiologia , Ratos Wistar , Fatores de Tempo , Bexiga Urinária/efeitos da radiação , Urotélio/efeitos da radiaçãoRESUMO
Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor. .
Assuntos
Animais , Masculino , Telefone Celular , Cistite/etiologia , Radiação Eletromagnética , Doenças da Bexiga Urinária/etiologia , Microscopia Eletrônica de Transmissão , Ratos Wistar , Lesões Experimentais por Radiação/etiologia , Fatores de Tempo , Bexiga Urinária/efeitos da radiação , Urotélio/efeitos da radiaçãoRESUMO
PURPOSE: To study the possible potentiation of the carcinogenic effects of ultraviolet radiation associated with an organophosphate pesticide. METHODS: Forty Wistar rats were assigned into four groups (n=10 each) randomized according to the procedures: group A received only UVR-B radiation; group B, UVR-B for eight weeks followed by a seven week period of pesticide exposure; group C, UVR-B + pesticide concomitantly: group D, only pesticide application. At the end of the fifth, tenth and fifteenth weeks the animals were photographed. Skin biopsy and histopathological study with Hematoxylin-Eosin were done on the fifteenth week. Statistical analysis with Fisher's and Sign (unilateral) tests, 5% value for significance. RESULTS: Macroscopic lesions in the group A evolved from the erythema to erythema + desquamation. The groups B and C, with the association of two carcinogens, and group D presented evolution to keratosis, with higher incidence in group D. The histology showed a significant increase in the severity of injuries when the UVR-B and the pesticide were applied simultaneously, leading to cellular atypia. CONCLUSIONS: Concurrent association of UVR-B to organophosphate pesticide produced more severe lesions microscopically, although this has not been so apparent macroscopically. In daily practice the clinical evaluation should be complemented with laboratory evaluation.
Assuntos
Cocarcinogênese , Organofosfatos/toxicidade , Praguicidas/toxicidade , Lesões Experimentais por Radiação/patologia , Neoplasias Cutâneas/patologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Seguimentos , Masculino , Doses de Radiação , Lesões Experimentais por Radiação/etiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Pele/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/complicaçõesRESUMO
Oscillating Low Frequency Electro-Magnetic Fields action on eye retina restoration in Rattus Norvegicus was studied in the present work. A beneficial effect of 3-Dimention Oscillating Low Frequency Electro-Magnetic Field was found for the specific values of Electro-Magnetic Field parameters. We found that eye retina damaged by radiation of the fundamental frequency harmonic of a YAG laser has recovered earlier and rehabilitated to the original 3D-state in the presence of OLFEMF, with the parameters listed below in the text. The results obtained were explained by the action of oscillating sub-macro-motions in the cells upon the metabolic processes in these cells.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Lasers/efeitos adversos , Lesões Experimentais por Radiação/etiologia , Retina/lesões , Retina/efeitos da radiação , Animais , Feminino , Masculino , Lesões Experimentais por Radiação/fisiopatologia , Ratos , Regeneração/efeitos da radiação , Retina/fisiologiaRESUMO
Nitric oxide (NO) is produced by various mammalian cells and plays a variety of regulatory roles in normal physiology and in pathological processes. This article provides evidence regarding the participation of NO in UVB-induced skin lesions and in the modulation of skin cell proliferation following UVB skin irradiation. Hairless mice were subjected to UVB irradiation for 3 hours and the skin evaluated immediately, 6 and 24 hours postirradiation. The skin lipid peroxidation, and NO levels evaluated by chemiluminescence and inducible nitric oxide synthase (iNOS) and nitrotyrosine immunolabelling increased significantly 24 hours after irradiation and decreased under the treatment with aminoguanidine (AG). On the other hand, cell proliferation markers, PCNA and VEGF showed a strong labelling index when AG was used. The data indicate that NO mediates, at least in part, the lipid peroxidation and protein nitration and also promotes the down regulation of factors involved in cell proliferation. This work shows that the NO plays an important role in the oxidative stress damage and on modulation of cell proliferation pathways in UVB irradiated skin.
Assuntos
Óxido Nítrico/biossíntese , Lesões Experimentais por Radiação/metabolismo , Pele/efeitos da radiação , Animais , Biomarcadores/metabolismo , Proliferação de Células/efeitos da radiação , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Guanidinas/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Masculino , Camundongos , Camundongos Pelados , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Tirosina/análogos & derivados , Tirosina/análise , Tirosina/imunologia , Raios Ultravioleta/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
CpG-oligodeoxynucleotide (ODN), a synthetic analog of bacteria DNA, has attracted attention because it activates cells of an adaptive immune system and the innate immune system. In this study, we investigated whether CpG-ODN has radioprotective effects, when administered after total-body irradiation (TBI). Mice were treated with 50 µg CpG-ODN via intraperitoneal injection (i.p) within 30 min, 24 h and 48 h after TBI. Our results showed that the survival rate was enhanced at various levels of TBI. The calculated dose reduction factor (DRF) was 1.2. Bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized the bone marrow damage induced by TBI. The data of the white blood cell (WBC) count, exogenous (CFU-S) and endogenous (endoCFU-S) colony forming unit-spleen count demonstrated that CpG-ODN reduced primitive hematopoietic stem cells damage and reconstituted hematopoiesis after TBI. Thus, we suggested that CpG-ODN had the potential to contribute to the improvement of the survival rate and limitation of myelosuppression induced by TBI.